POS0367 IMPROVEMENT OF INDIVIDUAL MUCOCUTANEOUS MANIFESTATIONS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS TREATED WITH ANIFROLUMAB
Authors: V. Werth, J. Wissmar, A. Strömbeck, R. Tummala, C. Kleoudis, M. Albulescu
Journal: Annals of the Rheumatic Diseases (2022)

Background Patients with cutaneous lupus erythematosus (CLE) experience disfiguring and painful lesions that can lead to psychological distress and significant impacts on quality of life. 1 Treatment of patients with systemic lupus erythematosus (SLE) with anifrolumab, a type I interferon receptor antagonist, was associated with CLE Disease Area and Severity Index–Activity (CLASI-A) improvements compared with placebo through Week 52 in the phase 3 TULIP-1 and TULIP-2 SLE trials. 2,3 CLASI assesses overall skin improvement and may be driven by erythema over the other components. 4 Objectives To better understand the effect of anifrolumab on mucocutaneous SLE manifestations by analyzing the individual domains of CLASI-A using pooled data from the TULIP trials. Methods TULIP-1 ( NCT02446912 ) and TULIP-2 ( NCT02446899 ) were randomized, double-blind, placebo-controlled, 52-week trials that evaluated efficacy and safety of intravenous anifrolumab administered every 4 weeks in patients with moderate to severe SLE despite standard therapy. 2,3 In a post hoc analysis, individual CLASI-A domains (erythema, scale/hypertrophy, alopecia, and mucosal) were assessed at Week 24 (time point chosen to ensure adequate duration for improvement in slow-remitting manifestations [eg, scale, alopecia]) in 2 patient subgroups: 1) the “chronic” mucocutaneous subgroup (resembling chronic/discoid CLE), defined as patients with a baseline erythema score ≥4 and scale score ≥2, and alopecia score ≥1 or baseline mucosal lesions or ulceration score of 1; and 2) the “extended” mucocutaneous subgroup (resembling all CLE subtypes), defined as patients who met the “chronic” criteria or those who had a baseline erythema score ≥8. Results Across the pooled TULIP trials, 360 patients received anifrolumab 300 mg and 366 patients received placebo. In patients with assessments at Week 24 in the “chronic” (anifrolumab n=58, placebo n=50) and “extended” (anifrolumab n=104, placebo n=96) subgroups, anifrolumab led to a greater mean percent reduction from baseline compared with placebo in erythema (chronic: −63.6% vs −39.9%; extended: −63.7% vs −41.2%) and scale/hypertrophy (chronic: −72.2% vs −42.6%; extended: −45.3% vs −7.3%). Anifrolumab-treated patients in both subgroups had no worsening in alopecia (chronic: 93.3% [56/60] vs 96.0% [48/50]; extended: 95.3% [102/107] vs 95.8% [92/96]) or mucous membrane (chronic: 95.0% [57/60] vs 96.0% [48/50]; extended: 96.3% [103/107] vs 94.8% [91/96]) from baseline vs placebo (Table 1). Table 1. Skin Responses at Week 24 Compared With Baseline Criteria, n (%) Chronic subgroup Extended subgroup Anifrolumab 300 mg (n=60) Placebo (n=50) Anifrolumab 300 mg (n=107) Placebo (n=96) Erythema score reduction ≥25% 53 (88.3) 32 (64.0) 93 (86.9) 68 (70.8) ≥50% 42 (70.0) 22 (44.0) 71 (66.4) 47 (49.0) ≥60% 34 (56.7) 18 (36.0) 61 (57.0) 32 (33.3) Scale/hypertrophy score reduction ≥10% 49 (81.7) 34 (68.0) 55 (51.4) 38 (39.6) ≥25% 47 (78.3) 30 (60.0) 53 (49.5) 34 (35.4) ≥50% 46 (76.7) 28 (56.0) 51 (47.7) 31 (32.3) No new/worsened lesions in any individual body area 44 (73.3) 26 (52.0) 81 (75.7) 56 (58.3) Alopecia ≥1-point decrease a 25 (41.7) 19 (38.0) 35 (32.7) 27 (28.1) No worsening 56 (93.3) 48 (96.0) 102 (95.3) 92 (95.8) Mucosal lesion/ulceration 1-point decrease b 25 (41.7) 13 (26.0) 39 (36.4) 23 (24.0) No worsening 57 (95.0) 48 (96.0) 103 (96.3) 91 (94.8) a If baseline score ≥1. b If baseline score =1. Conclusion In the phase 3 TULIP trials, SLE patients with mucocutaneous manifestations treated with anifrolumab experienced numerical improvements in erythema and scale/hypertrophy and no worsening in alopecia or mucous membrane CLASI-A domains compared with placebo, regardless of whether skin disease was classified by chronic or extended definitions. These encouraging data support further evaluation of anifrolumab in patients with CLE. References [1]Klein R. J Am Acad Dermatol. 2011;64:849–58. [2]Furie RA. Lancet Rheumatol . 2019;1:e208–19. [3]Morand EF. N Engl J Med. 2020;382:211–21. [4]Albrecht J. J Invest Dermatol. 2005;125:889–94. Acknowledgements Writing assistance by Naomi Atkin (Fishawack Health). This study was sponsored by AstraZeneca. Disclosure of Interests Victoria Werth Consultant of: Celgene, Medimmune, Resolve, Genentech, Idera, Janssen, Lilly, Pfizer, Biogen, BMS, Gilead, Amgen, Medscape, Nektar, Incyte, EMD Sorona, CSL Behring, Principia, Crisalis, Viela Bio, Argenx, Kwoya Kirin, Regeneron, AstraZeneca, Abbvie, Octapharma, GSK, Cugene, UCB, Corcept, Beacon Bioscience, Rome Pharmaceuticals, Horizon, Merck, Kezar, Sanofi, Bayer, Akari, Grant/research support from: Celgene, Janssen, Pfizer, Biogen, Gilead, Corbus Pharmaceuticals, Genentech, AstraZeneca, Viela, Syntimmune, Amgen, Regeneron, Argenx, CSL Behring, Ventus, q32 Bio, BMS, Jenny Wissmar Shareholder of: AstraZeneca, Employee of: AstraZeneca, Anna Strömbeck Employee of: AstraZeneca, Raj Tummala Shareholder of: AstraZeneca, Employee of: AstraZeneca, Christi Kleoudis Shareholder of: AstraZeneca, Employee of: AstraZeneca, Marius Albulescu Shareholder of: AstraZeneca Ltd, Consultant of: UCB, Kymab Ltd, Employee of: AstraZeneca Ltd